Transesterification is a process whereby an ester group's functionality is modified by exchanging groups with a suitable reagent (such as an alcohol). This process is well-known as disclosed in March, Advanced Organic Chemistry, 2d Ed, section 0-25 pp 365-7, 1977 McGraw Hill, New York, N.Y.; and Morrison and Boyd, Organic Chemistry, 4th Ed, pp 831 and 836-8, 1983 Allyn Bacon, Inc. Boston, Mass. The process may often require high temperatures, such as 150° C. or above, and a relatively high amount of the catalyst(s). Many transesterification reactions are base catalyzed, which is accomplished by assisting in the removal a proton from the reagent (such as an alcohol) making it more nucleophilic to undergo transesterification. Transesterification is easily identified as an equilibrium process benefiting from the removal of byproducts to achieve higher yields of the desired product(s). These exemplary characteristics of the process can often limit its commercial utilization—especially in relation to the various reactants and/or reagents utilized where the stability of the reaction can be compromised.
Transesterification of highly reactive unsaturated esters, such as 1,1-disubstituted alkene compounds which have one or more ester groups as substituents, can be problematic under some well-known transesterification conditions. 1,1-Disubstituted alkene compounds readily undergo anionic polymerization in the presence of weak bases and nucleophiles under ambient conditions, as well as free radical initiated polymerization and auto-polymerization upon exposure to elevated temperatures for prolonged periods of time. The transesterification of these types of reactive species precludes employing base catalyzed transesterification and the use of basic and/or nucleophilic catalysts. Malofsky et al. WO 2013/059473, incorporated herein by reference in its entirety for all purposes, discloses the preparation of multifunctional methylene malonates by multiple synthetic schemes. One disclosed process involves reacting a methylene malonate with a polyol in the presence of a catalyst to prepare compounds wherein one of the ester groups on the methylene malonates undergoes transesterification to react with the polyol and form multifunctional compounds (multifunctional meaning the presence of more than one methylene malonate core unit).
The compounds formed via transesterification have two or more methylene malonate moieties bonded to the oxygen atoms on the polyol. Additionally, the use of enzyme catalysis is disclosed. Enzymatic catalysts work well but can be expensive and recyclability attempts often result in drastically deficient or no observable catalytic activity for these transesterification reactions. The use of expensive catalysts and lack of recyclability can restrict scale-up opportunities concerning these monomers. The alternative process for preparing various ester and diester 1,1-disubstituted alkene compounds is to first form the precursor 1,1-diester alkylate compounds (i.e., the non-reactive or anionically polymerizable compounds). This is a multistep process and complex separation processes may be required depending on the monomers synthesized (see Malofsky et al., U.S. Pat. Nos. 8,609,885 and 8,884,051). Additionally, each 1,1-disubstituted alkene compound requires different catalytic cracking and product separation conditions. This suggests that multiple reactors and isolated separation hardware modules are required for each individual compound. Ultimately, under these described processing conditions, the capital and change over costs for manufacturing different 1,1-disubstituted alkene compounds in viable commercial quantities would be quite high.
Ester containing compounds that contain reactive functional groups (such as 1,1-disubstituted alkenes) can undergo undesired side reactions under typical transesterification reaction conditions. Exemplary side reactions include polymerization through the reactive alkene functionality via free radical and/or anionic mechanisms, Michael addition of reagent alcohol to the alkene functional group, Michael addition of the reaction byproduct alcohol with the alkene functionality, and the like. Exemplary classes of compounds that can undergo such side reactions include 1,1-disubstituted alkenes (such as methylene malonates) wherein the substituents are electron withdrawing, cyanoacrylates, acrylates, methacrylates, and the like. The possibility of such side reactions can limit the use of transesterification for such reactive compounds. Furthermore, the implementation of base catalysts for transesterification of such reactive systems is not possible, as the nucleophilic nature of the catalyst would anionically initiate polymerization—a competing reaction to transesterification if that were to occur.
Thus, a method for transesterifying ester containing reactive compounds (including 1,1-disubstituted alkene compounds) is needed which utilizes a cost efficient and compatible catalyst system. Additionally, a process that efficiently transesterifies compounds that may alternatively undergo undesired side reactions via typical transesterification conditions is needed. Also needed is an improved, more defined synthetic or manufacturing process for preparing multiple 1,1-disubstituted alkene compounds with varied ester substituent groups or monomer functionality.